2013 NMO and TM Research Symposium
January 12, 2013 | Dallas, Texas
Sponsored by the UT Southwestern Department of Neurology and the Office of Continuing Medical Education
Welcome and Introduction
The symposium began with an introduction by Benjamin Greenberg, MD, MHS, Assistant Professor in the Department of Neurology and Neurotherapeutics and the Department of Pediatrics. Dr. Greenberg is also the Director of the Transverse Myelitis and Neuromyelitis Optica Program, Director of the Pediatric Demyelinating Disease Program, and Deputy Director of the Multiple Sclerosis Program. The goal of Dr. Greenberg’s presentation was to provide a basic understanding of the nervous system and immune system and the relationship between these two systems in an autoimmune, demyelinating disease. Beginning on the seventh slide, Dr. Greenberg introduces an analogy of a stereo system to explain the effects of damage to the wires (neurons) in the nervous system. Wires of a stereo system contain an insulating material that enables them conduct the electricity effectively. Similarly, neurons have a coating called the myelin sheath that accomplishes the same goal. If a wire is cut or the insulation around the wire is damaged in the stereo system, the signals will not be sent to the speakers properly and the stereo system will not work correctly. Similarly, if the wires of the nervous system are damaged, the signals that they transmit will not be sent correctly. To explain an autoimmune, demyelinating disease, Dr. Greenberg expanded on the stereo model by comparing the immune system to a house cat. A house cat has been raised to hunt mice, which represent foreign invaders in your body. The immune system’s response to foreign invaders is what keeps one healthy and well. However, sometimes the cat will chew on things in the house that are not mice and this can be destructive to personal belongings. This represents autoimmune diseases in which the immune system will attack things within thie body that are important and are not foreign invaders. For autoimmune, demyelinating diseases, the immune system views the myelin sheath on the neurons in the central nervous system as foreign invaders and causes demyelination, destruction of the myelin sheath. To refer back to the analogy of a cat and the stereo system, this would be analogous to the cat chewing on the wires of the stereo system. The goal of research focused on these diseases is to determine which cat is chewing on the wires of the stereo system and how to stop this action to eliminate further damage.
Dr. Greenberg provided an overview of the rare neuroimmune disorders in this spectrum and described which “wires” are being affected in which disease and the incidence of relapse in each of these diseases. He also detailed the advancements that have been made in the understanding of NMO through the findings of the NMO IgG, an antibody specific to patients diagnosed with NMO.
Dr. Greenberg finished his introduction by providing a brief description of the necessity of repository-style research projects in the research of these diseases. He mentioned Donald Rumsfeld’s quote to highlight the “unknown unknowns”, or the things that researchers don’t know to investigate yet. However, the repository-style research projects will allow researchers access to large amounts of samples and data in the case that future researchers discover that they need to research something that has not been investigated previously. For instance, Dr. Greenberg described that right now when drawing blood, the red-top tubes are of most interest to him. However, as research progresses, he may find that the yellow-top tubes are what we should be looking at. At this point he will be able to go back to the repository and will have a large amount of these yellow-top tubes that he can use in his research. As researchers are furiously searching for the causes of NMO and TM, the biorepositories allow them to look into various aspects of the disease to search for a better understanding of these diseases to better treat and hopefully cure these conditions.
The Role of T Lymphocytes in NMO and MS
Dr. Stuve is an Associate Professor in the Department of Neurology and Neurotherapeutics at UT Southwestern, an Associate Professor in the Graduate Program in the Department of Immunology at UT Southwestern, and the Chief in the Neurology Section in the VA North Texas Health Care Systems. Dr. Stuve has dedicated much of his time to investigating the role of one “cat” as described by Dr. Greenberg, T-cells, in Multiple Sclerosis (MS) and NMO. Through Dr. Stuve’s work, the role of T-cells has become more apparent in NMO than was previously expected. However, the fact that patients diagnosed with NMO that have been treated with Tysabri (Natalizumab), which reduces T-cells, still experience relapses has provided some insight into the involvement of T-cells in NMO. Dr. Stuve explained that while there are T-cells which may play a role in the disease, there are other T-cells, known as T regulatory (Treg) cells, which may play a role in the protection of the nervous system and these cells may be targeted by therapies such as Tysabri, which might explain their lack of effectiveness. Further research of the role of the Treg cells has led to recent investigation of a specific interleukin, known as IL-6, and its role in NMO. Dr. Stuve’s research illustrates not only the complexity of these diseases, but also the improvements being made in developing more effective treatment options for NMO.
Dysregulation of B Cells in Clinically Isolated Syndrome and Multiple Sclerosis
Dr. Monson is an Associate Professor in the Department of Neurology and Neurotherapeutics and in the Graduate Program in the Department of Immunology at UT Southwestern. Dr. Monson has made considerable progress to a better understanding of MS and TM through her work with another “cat” as described by Dr. Greenberg, B-cells. Dr. Monson illustrated the complexity of these conditions in terms of recognizing B-cells that may play a role in TM and MS. She described a B-cell that is detected in patient diagnosed with TM and MS, but not present in patients diagnosed with Optic Neuritis (ON). Also, it has been seen that the levels of this B-cell in spinal fluid and blood are greater in TM patients than MS patients. Dr. Monson also discussed a “signature” on B-cells from spinal fluid that her lab has been investigating. This “signature” was determined to be unique to patients diagnosed with clinically definite MS in comparison to healthy control subjects. Furthermore, it has been determined that the presence of this “signature” can predict conversion of patients diagnosed with TM or ON to MS with high accuracy. This finding has the potential to revolutionize the diagnosis of MS and ensure that patients are treated earlier. Dr. Monson has been utilizing the samples and data obtained through biorepositories to fuel her research and continues to use these samples to validate the implications of the B-cell “signature”.
Cognition and NMO/TM
Dr. Harder is an Assistant Professor in the Departments of Neurology and Neurotherapeutics and Psychiatry at UT Southwestern and a Neuropsychologist at Children’s Medical Center at Dallas. Dr. Harder has previously shared her work on cognition in transverse myelitis on SRNA blog. During Dr. Harder’s presentation, she expanded on the information that she previously provided by including research on NMO and cognitive function. Dr. Harder’s findings have challenged the previously accepted notion of the lack of brain involvement in both NMO and TM by illustrating cognitive impairment in patients diagnosed with these diseases. The research being conducted by Dr. Harder is important to further research and treat patients diagnosed with these diseases.
Current Studies and Repository Efforts
The final presentation featured the repositories and studies that are currently collecting samples and data that have enabled the UT Southwestern researchers to investigate these diseases and make progress toward developing effective treatments. Samuel Hughes, a Research Study Coordinator from the UT Southwestern Neuroimmunology Program, introduced two studies that have been established at our center. The first study discussed was the Accelerated Cure Project for Multiple Sclerosis Repository, which is a nation-wide collection of biological samples and data from patients diagnosed multiple sclerosis and selected demyelinating diseases, as well as healthy controls that can be accessed by researchers investigating these conditions. The second study Sam discussed was the UT Southwestern Biorepository. The purpose of this repository is to collect biological specimens from patients diagnosed with a demyelinating disease and healthy controls and work with researchers to acquire samples that may be requested for particular studies being conducted. Finally, Morgan McCreary, a Research Technician from the UT Southwestern Neuroimmunology Program, discussed a new study that has recently been established at UT Southwestern, the Longitudinal Study of NMO and Related Diseases. This study is the first to examine patients diagnosed with NMO, NMO Spectrum Disorder, TM, and ON on a routine basis to develop a natural history repository for access by researchers investigating these diseases.
